Modulation of the canonical Wnt signaling pathway in bone and cartilage

Modulation of the canonical Wnt signaling pathway in bone and cartilage

Miclea, R.L.

Citation

Miclea, R. L. (2011, November 30). Modulation of the canonical Wnt signaling pathway in bone and cartilage. Retrieved from https://hdl.handle.net/1887/18153

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/18153

Note: To cite this publication please use the final published version (if applicable).

List of publications

L IST OF PUBLICATIONS

Miclea RL, Robanus-Maandag EC, Goeman JJ, Finos L, Bloys H, Oostdijk W, Löwik CW, Wit JM, Karperien M – Inhibition of Gsk3β in cartilage induces osteoarthritic features through activation of the canonical Wnt signaling pathway. Osteoarthritis Cartilage, 2011 Aug 27. [Epub ahead of print].

Miclea RL, van der Horst G, Robanus-Maandag EC, Lowik CW, Oostdijk W, Wit JM, Karperien M – Apc bridges Wnt/β-catenin and BMP signaling during osteoblast diffe- rentiation of KS483 cells. Exp Cell Res. 2011 Jun 10;317(10):1411-21

Miclea RL, Karperien M, Langers AM, Robanus-Maandag EC, van Lierop A, van der Hiel B, Stokkel MP, Ballieux BE, Oostdijk W, Wit JM, Vasen HF, Hamdy NA – APC mutations are associated with increased bone mineral density in patients with familial adenoma- tous polyposis. J Bone Miner Res. 2010 Dec;25(12):2624-32

Miclea RL, Karperien M, Bosch CA, van der Horst G, van der Valk MA, Kobayashi T, Kronenberg HM, Rawadi G, Akçakaya P, Lowik CW, Fodde R, Wit JM, Robanus- Maandag EC – Adenomatous polyposis coli-mediated control of β-catenin is essential for both chondrogenic and osteogenic differentiation of skeletal precursors. BMC Dev Biol. 2009 Apr;9(1):26

Miclea RL, Phillip M, Sävendahl L, Wit JM – The 7th ESPE Growth Plate Working Group Symposium – EUROGROP June 27th 2007, Helsinki, Finland. Pediatr Endocrinol Rev.

2007 Dec;5(2):680-5

Hendriks J, Miclea RL, Schotel R, Karperien M, Riesle J, van Blitterswijk CA – Primary chondrocytes enhanced their cartilage tissue formation when co-cultured with dermal fibroblasts, 3T3 fibroblasts and embryonic stem cells. Soft Matter. 2010 Mar 6:5080- 5088

Hoogendam J, Parlevliet E, Miclea R, Löwik CW, Wit JM, Karperien M – Novel early target genes of PTHrP in chondrocytes. Endocrinology. 2006 Jun;147(6):3141-52

Miclea RL, Robanus-Maandag EC, Lowik CW, Oostdijk W, Fodde R, Wit JM, Karperien M

– Adenomatous polyposis coli-gene dosage controls β-catenin-mediated differentiation

of skeletal precursors. Manuscript in preparation.

Curriculum vitae

C URRICULUM VITAE

The author of this thesis was born on May 24

, 1979 in Oradea, Romania. He attended secondary school at the “Mihai Eminescu” high school in Oradea, where he got his Romanian Baccalaureate diploma in June 1998. He then started his study in Medicine at the “Iuliu Haţieganu” University of Medicine and Pharmacy in Cluj-Napoca, Roma- nia, where he received his MD diploma in September 2004. During his medical study he performed a 3-months research project at the subdivision of Pediatric Endocrinol- ogy of the Leiden University Medical Center (LUMC) under the supervision of Prof. Dr.

J. M. Wit and Dr. M. Karperien investigating possibilities to enhance the differentiation

of KS483 cells into chondrocytes. From March 2005 until May 2010 he performed re-

search for his present PhD project at the subdivision of Pediatric Endocrinology of the

LUMC under the supervision of Prof. Dr. J. M. Wit, Dr. M. Karperien and Dr. E. C. Roba-

nus-Maandag. For the research he conducted during his PhD program he received

several fellowships and awards: in 2005 a Short Time Research Fellowship from the

European Society for Pediatric Endocrinology (ESPE, Lyon, FR); in 2006 a Travel Award

from the ESPE (Rotterdam, NL); in 2007 a Young Investigator Award from the European

Calcified Tissue Society (ECTS, Copenhagen, DK); in 2008 a Travel Award from the ECTS

(Barcelona, Spain). He began his training in radiology in May 2010 in the LUMC, under

the supervision of Prof. Dr. J. L. Bloem.

Dankwoord

D ANKWOORD

It takes only two to tango but it surely takes a hundred to finalize a PhD thesis. If you are reading these lines you most likely have contributed directly or indirectly to this thesis. Therefore thank you! I will be forever grateful to you all! I would like to use this opportunity to personally thank some of you.

My promotor, Prof. Dr. Jan Maarten Wit. Jan Maarten, thank you very much for the opportunity you gave me to conduct a PhD study under your supervision. Your scientific enthusiasm and curiosity have inspired me throughout the years! You gave me a lot of freedom in my research, yet you were always carefully guiding and encour- aging what turned out to be a rewarding project.

My co-promotor, Dr. Marcel Karperien. Marcel, I have learned so much from you (too much to be named here), for which I express my deepest gratitude. In the first years from close by, later from Twente, you always stimulated me to get the most from my experiments. The foundation of this thesis lays in your ideas.

My co-promotor, Dr. Els Robanus-Maandag. Els, many thanks for “adopting” me after Marcel left for Twente. Your accuracy and critical point-of-view have always had a positive effect on the interpretation of my results.

Dr. Neveen Hamdy, thank you for supervising the BOMFAP study with your great experience in clinical research.

Dr. Wilma Oostdijk, thank you for your interest in my project and for your con- structive feedback.

I’d like to thank my Kinder-ENDO research colleagues Hermine, Joyce, Remco and Sandy, who ensured that I was constantly engaged and entertained along the way.

Special thanks to Jakomijn for initiating me in the bio-medical research lab.

I thank my office mates, Geertje and Jimmy for their contribution to the cheerful, yet productive atmosphere we had the luck to work in.

I would like to thank the people from the ENDO-lab for their support and gezel- ligheid. Annemiek, Antoon, Chris, Christel, Claudia, Edwin, Eric, Gabri, Guido, Hanna, Henny, Henry, Ineke, Isabel, Ivo, Janna, Janny, Judith, Karien, Laura, Maggy, Martiene, Patrick, Petra, Thomas, Rutger, Trea, Vicky have all made me feel at home in the EN- DO-lab although I was a kinder-AIO. Special thanks to Hetty for familiarizing me with several molecular biology techniques and to Lianne for her histological expertise.

I am grateful to Prof. Dr. Clemens Löwik, Prof. Dr. Hans Romijn and Prof. Dr. Jan Smit for their valuable comments and hospitality.

I would like to definitely acknowledge all the FAP patients that volunteered to

participate in the BOMFAP study as well as Prof. Dr. Hans Vasen for helpful discussions

during the course of this clinical study.

Dankwoord

186

Thanks to the secretaries of the Pediatrics department for their assistance, espe- cially Mirjam Vollebregt, who always provided a prompt answer to my administrative dilemmas.

My appreciation also goes to my two Bachelor students that I had the chance to supervise. Both Celia and Pinar impressed me with their determination, that I’m sure will help them a lot in their future careers.

I’d also like to thank my two paranymphs, Jeroen and Michel. I am very happy to have such friends besides me on this memorable day. I hope you both feel the same.

în final aş dori să mă adresez familiei mele fără de care această carte ar fi fost infinit mai săracă. Socrilor mei le mulţumesc pentru suportul şi bunătatea lor cu care ne înconjoară de peste ţări şi de aproape.

Nico, Dinu, Alex, Roxi, Tuşa, Iulia şi Muşi, deşi departe, unii nedrept de departe, dragostea voastră m-a ajutat, poate fără să ştiţi, să duc la bun sfârşit acest proiect.

Părinţilor mei le voi fi mereu îndatorat. Mami şi Tati, m-aţi ajutat să mă ridic iar apoi m-aţi încurajat să îmi urmez drumul ce-l doresc în viaţă, deşi asta a însemnat să mă vedeţi plecat. Căldura şi dragostea voastră necondiţionată m-au sprijinit şi impulsionat mereu.

Sara, îngeraşul meu, sper să îţi placă acum albastrul copertei şi să fii mândră de tati peste ani când sper să vrei să citeşti câteva rânduri din această teză. în prezenţa ta, tot restul devine nesemnificativ.

Cristina, eşti farul meu pe furtună si pe cer senin, dimineaţa şi seara, ieri şi mâine.

îţi dai seama că la câtă apă e în Olanda, fără lumina ta m-aş fi rătăcit demult. îţi

mulţumesc pentru că eşti. Te iubesc din tot sufletul meu!